Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: A new mechanism for ALS

EMBO Journal

Volumn 34, Issue 21, 2015, Pages 2633-2651

  Emde, Anna ^a   Eitan, Chen ^a   Liou, Lee Loung ^b   Libby, Ryan T ^c   Rivkin, Natali ^a   Magen, Iddo ^a   Reichenstein, Irit ^a   Oppenheim, Hagar ^a   Eilam, Raya ^a   Silvestroni, Aurelio ^b   Alajajian, Betty ^b   Ben Dov, Iddo Z ^d   Aebischer, Julianne ^e   Savidor, Alon ^a   Levin, Yishai ^a   Sons, Robert ^f   Hammond, Scott M ^f   Ravits, John M ^c,g   Möller, Thomas ^b   Hornstein, Eran ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c BENAROYA RESEARCH INSTITUTE   (United States)

^d HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^e EPFL   (Switzerland)

^f UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

ALS; DICER; microRNA; neurodegeneration; stress

Indexed keywords

ARGONAUTE 2 PROTEIN; DICER; ENOXACIN; INITIATION FACTOR 2ALPHA; INITIATION FACTOR 5A; LET 7B PROTEIN; LONG UNTRANSLATED RNA; MICRORNA; MICRORNA 10B; MICRORNA 124; MICRORNA 132; MICRORNA 9; MIRNA 103; MIRNA 138; MIRNA 218; MIRNA 30A; MIRNA 30C; PROTEIN; UNCLASSIFIED DRUG; COPPER ZINC SUPEROXIDE DISMUTASE; DEAD BOX PROTEIN; DICER1 PROTEIN, HUMAN; RIBONUCLEASE III; SOD1 PROTEIN, HUMAN; SOD1 PROTEIN, MOUSE; SUPEROXIDE DISMUTASE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; BIOGENESIS; CATALYSIS; CELLULAR STRESS SIGNAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DISEASE COURSE; DOWN REGULATION; DRUG EFFECT; EMBRYO; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; FEMALE; GAIT; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN SITU HYBRIDIZATION; IN VITRO STUDY; IN VIVO STUDY; LINEAR ENERGY TRANSFER; MALE; MOTONEURON; MOTOR CORTEX; MOTOR PERFORMANCE; NERVE CELL DEGENERATION; NEUROMUSCULAR FUNCTION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; RNA ANALYSIS; RNA HYBRIDIZATION; RNA SYNTHESIS; ROTAROD TEST; SCORING SYSTEM; SIGNAL TRANSDUCTION; TRANSIENT TRANSFECTION; UPREGULATION; WEIGHT REDUCTION; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CELL GRANULE; GENETICS; HEK293 CELL LINE; METABOLISM; NUCLEOTIDE SEQUENCE; PATHOLOGY; PHYSIOLOGICAL STRESS; PRECLINICAL STUDY; RNA INTERFERENCE; RNA PROCESSING; TRANSGENIC MOUSE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BASE SEQUENCE; CYTOPLASMIC GRANULES; DEAD-BOX RNA HELICASES; DOWN-REGULATION; DRUG EVALUATION, PRECLINICAL; ENOXACIN; FEMALE; HEK293 CELLS; HUMANS; MALE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICRORNAS; MOTOR NEURONS; RIBONUCLEASE III; RNA INTERFERENCE; RNA PROCESSING, POST-TRANSCRIPTIONAL; STRESS, PHYSIOLOGICAL; SUPEROXIDE DISMUTASE; SUPEROXIDE DISMUTASE-1;

EID: 84946489622     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201490493     Document Type: Article

References (105)

1. Anderson P, Kedersha N, (2008) Stress granules: the Tao of RNA triage. Trends Biochem Sci 33: 141-150
2. Anderson P, Kedersha N, (2009) RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 10: 430-436
3. Aulas A, Stabile S, Vande Velde C, (2012) Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP. Mol Neurodegener 7: 54
4. Baron DM, Kaushansky LJ, Ward CL, Sama RR, Chian RJ, Boggio KJ, Quaresma AJ, Nickerson JA, Bosco DA, (2013) Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics. Mol Neurodegener 8: 30
5. Blobel G, Sabatini D, (1971) Dissociation of mammalian polyribosomes into subunits by puromycin. Proc Natl Acad Sci USA 68: 390-394
6. Bosco DA, Lemay N, Ko HK, Zhou H, Burke C, Kwiatkowski TJ Jr, Sapp P, McKenna-Yasek D, Brown RH Jr, Hayward LJ, (2010) Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum Mol Genet 19: 4160-4175
7. Buchan JR, Parker R, (2009) Eukaryotic stress granules: the ins and outs of translation. Mol Cell 36: 932-941
8. Buratti E, De Conti L, Stuani C, Romano M, Baralle M, Baralle F, (2010) Nuclear factor TDP-43 can affect selected microRNA levels. FEBS J 277: 2268-2281
9. Campos-Melo D, Droppelmann CA, He Z, Volkening K, Strong MJ, (2013) Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels. Mol Brain 6: 26
10. Cassidy JJ, Jha AR, Posadas DM, Giri R, Venken KJ, Ji J, Jiang H, Bellen HJ, White KP, Carthew RW, (2013) miR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor. Cell 155: 1556-1567
11. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R, (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436: 740-744
12. Costa-Mattioli M, Gobert D, Stern E, Gamache K, Colina R, Cuello C, Sossin W, Kaufman R, Pelletier J, Rosenblum K, Krnjevic K, Lacaille JC, Nader K, Sonenberg N, (2007) eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell 129: 195-206
13. Daigle JG, Lanson NA Jr, Smith RB, Casci I, Maltare A, Monaghan J, Nichols CD, Kryndushkin D, Shewmaker F, Pandey UB, (2013) RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Hum Mol Genet 22: 1193-1205
14. De Felice B, Annunziata A, Fiorentino G, Borra M, Biffali E, Coppola C, Cotrufo R, Brettschneider J, Giordana ML, Dalmay T, Wheeler G, D'Alessandro R, (2014) miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic amyotrophic lateral sclerosis patients. Neurogenetics 15: 243-253
15. Dewey CM, Cenik B, Sephton CF, Dries DR, Mayer P III, Good SK, Johnson BA, Herz J, Yu G, (2011) TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor. Mol Cell Biol 31: 1098-1108
16. Dewey CM, Cenik B, Sephton CF, Johnson BA, Herz J, Yu G, (2012) TDP-43 aggregation in neurodegeneration: are stress granules the key? Brain Res 1462: 16-25
17. Dini Modigliani S, Morlando M, Errichelli L, Sabatelli M, Bozzoni I, (2014) An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA-FUS regulatory circuitry. Nat Commun 5: 4335
18. Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C, (2010) ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J 29: 2841-2857
19. Droppelmann CA, Wang J, Campos-Melo D, Keller B, Volkening K, Hegele RA, Strong MJ, (2013) Detection of a novel frameshift mutation and regions with homozygosis within ARHGEF28 gene in familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14: 444-451
20. Droppelmann CA, Campos-Melo D, Ishtiaq M, Volkening K, Strong MJ, (2014) RNA metabolism in ALS: when normal processes become pathological. Amyotroph Lateral Scler Frontotemporal Degener 15: 321-336
21. Emde A, Hornstein E, (2014) miRNAs at the interface of cellular stress and disease. EMBO J 33: 1428-1437
22. Esmaeili MA, Panahi M, Yadav S, Hennings L, Kiaei M, (2013) Premature death of TDP-43 (A315T) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis. Int J Exp Pathol 94: 56-64
23. Freischmidt A, Muller K, Ludolph AC, Weishaupt JH, (2013) Systemic dysregulation of TDP-43 binding microRNAs in amyotrophic lateral sclerosis. Acta Neuropathol Commun 1: 42
24. Fujimura K, Kano F, Murata M, (2008) Identification of PCBP2, a facilitator of IRES-mediated translation, as a novel constituent of stress granules and processing bodies. RNA 14: 425-431
25. Fujimura K, Katahira J, Kano F, Yoneda Y, Murata M, (2009) Selective localization of PCBP2 to cytoplasmic processing bodies. Biochim Biophys Acta 1793: 878-887
26. Gal J, Zhang J, Kwinter DM, Zhai J, Jia H, Jia J, Zhu H, (2010) Nuclear localization sequence of FUS and induction of stress granules by ALS mutants. Neurobiol Aging 32: 2323. e27-40
27. Gascon E, Gao FB, (2014) The emerging roles of microRNAs in the pathogenesis of frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum disorders. J Neurogenet 28: 30-40
28. Gascon E, Lynch K, Ruan H, Almeida S, Verheyden JM, Seeley WW, Dickson DW, Petrucelli L, Sun D, Jiao J, Zhou H, Jakovcevski M, Akbarian S, Yao WD, Gao FB, (2014) Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med 20: 1444-1451
29. Gill A, Kidd J, Vieira F, Thompson K, Perrin S, (2009) No benefit from chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using a standard mouse model of familial ALS. PLoS ONE 4: e6489
30. Gitcho MA, Baloh RH, Chakraverty S, Mayo K, Norton JB, Levitch D, Hatanpaa KJ, White CL III, Bigio EH, Caselli R, Baker M, Al-Lozi MT, Morris JC, Pestronk A, Rademakers R, Goate AM, Cairns NJ, (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63: 535-538
31. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R, (2004) The microprocessor complex mediates the genesis of microRNAs. Nature 432: 235-240
32. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, Chen W, Zhai P, Sufit RL, Siddique T, (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 1772-1775
33. Haase AD, Jaskiewicz L, Zhang H, Laine S, Sack R, Gatignol A, Filipowicz W, (2005) TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. EMBO Rep 6: 961-967
34. Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills AM, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R Jr, Chen A, Hornstein E, (2010) miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci USA 107: 13111-13116
35. Hinnebusch AG, (2005) eIF2alpha kinases provide a new solution to the puzzle of substrate specificity. Nat Struct Mol Biol 12: 835-838
36. Hornstein E, Shomron N, (2006) Canalization of development by microRNAs. Nat Genet 38 (Suppl): S20-S24
37. Igaz LM, Kwong LK, Lee EB, Chen-Plotkin A, Swanson E, Unger T, Malunda J, Xu Y, Winton MJ, Trojanowski JQ, Lee VM, (2011) Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Investig 121: 726-738
38. Inukai S, Slack F, (2013) MicroRNAs and the genetic network in aging. J Mol Biol 425: 3601-3608
39. Jaarsma D, Haasdijk ED, Grashorn JA, Hawkins R, van Duijn W, Verspaget HW, London J, Holstege JC, (2000) Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates motoneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1. Neurobiol Dis 7: 623-643
40. Jiang J, Lee EJ, Gusev Y, Schmittgen TD, (2005) Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res 33: 5394-5403
41. Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA, (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40: 572-574
42. Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ, Cho WG, Kleinman ME, Ponicsan SL, Hauswirth WW, Chiodo VA, Kariko K, Yoo JW, Lee DK, Hadziahmetovic M, Song Y, Misra S, Chaudhuri G, Buaas FW, Braun RE, Hinton DR, et al, (2011) DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471: 325-330
43. Kawahara Y, Mieda-Sato A, (2012) TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc Natl Acad Sci USA 109: 3347-3352
44. Kedersha NL, Gupta M, Li W, Miller I, Anderson P, (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147: 1431-1442
45. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, Golan DE, Anderson P, (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151: 1257-1268
46. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, Scheuner D, Kaufman RJ, Golan DE, Anderson P, (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169: 871-884
47. Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, et al, (2013) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495: 467-473
48. Kim HJ, Raphael AR, LaDow ES, McGurk L, Weber RA, Trojanowski JQ, Lee VM, Finkbeiner S, Gitler AD, Bonini NM, (2014) Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet 46: 152-160
49. Koval ED, Shaner C, Zhang P, du Maine X, Fischer K, Tay J, Chau BN, Wu GF, Miller TM, (2013) Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum Mol Genet 22: 4127-4135
50. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, et al, (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323: 1205-1208
51. Lee Y, Hur I, Park SY, Kim YK, Suh MR, Kim VN, (2006) The role of PACT in the RNA silencing pathway. EMBO J 25: 522-532
52. Lee HY, Doudna JA, (2012) TRBP alters human precursor microRNA processing in vitro. RNA 18: 2012-2019
53. Lee HY, Zhou K, Smith AM, Noland CL, Doudna JA, (2013) Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing. Nucleic Acids Res 41: 6568-6576
54. Leung AK, Calabrese JM, Sharp PA, (2006) Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules. Proc Natl Acad Sci USA 103: 18125-18130
55. Leung AK, Sharp PA, (2007) microRNAs: a safeguard against turmoil? Cell 130: 581-585
56. Leung AK, Sharp PA, (2010) MicroRNA functions in stress responses. Mol Cell 40: 205-215
57. Li CH, Ohn T, Ivanov P, Tisdale S, Anderson P, (2010) eIF5A promotes translation elongation, polysome disassembly and stress granule assembly. PLoS ONE 5: e9942
58. Li Y, Lin L, Li Z, Ye X, Xiong K, Aryal B, Xu Z, Paroo Z, Liu Q, He C, Jin P, (2012) Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2. Cell Metab 15: 895-904
59. Li J, Sung M, Rutkove SB, (2013a) Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice. PLoS ONE 8: e65976
60. Li YR, King OD, Shorter J, Gitler AD, (2013b) Stress granules as crucibles of ALS pathogenesis. J Cell Biol 201: 361-372
61. Ling SC, Polymenidou M, Cleveland DW, (2013) Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79: 416-438
62. Liu-Yesucevitz L, Bilgutay A, Zhang YJ, Vanderweyde T, Citro A, Mehta T, Zaarur N, McKee A, Bowser R, Sherman M, Petrucelli L, Wolozin B, (2010) Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue. PLoS ONE 5: e13250
63. Ma E, MacRae IJ, Kirsch JF, Doudna JA, (2008) Autoinhibition of human dicer by its internal helicase domain. J Mol Biol 380: 237-243
64. MacLean B, Tomazela DM, Shulman N, Chambers M, Finney GL, Frewen B, Kern R, Tabb DL, Liebler DC, MacCoss MJ, (2010) Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26: 966-968
65. McDonald KK, Aulas A, Destroismaisons L, Pickles S, Beleac E, Camu W, Rouleau GA, Vande Velde C, (2011) TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Hum Mol Genet 20: 1400-1410
66. Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C, Rossi S, Setien F, Casanovas O, Simo-Riudalbas L, Carmona J, Carrere J, Vidal A, Aytes A, Puertas S, Ropero S, Kalluri R, Croce CM, Calin GA, Esteller M, (2011) Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci USA 108: 4394-4399
67. Melo CA, Melo SA, (2014) MicroRNA biogenesis: dicing assay. Methods Mol Biol 1182: 219-226
68. Mendell JT, Olson EN, (2012) MicroRNAs in stress signaling and human disease. Cell 148: 1172-1187
69. Meyerowitz J, Parker SJ, Vella LJ, Ng D, Price KA, Liddell JR, Caragounis A, Li QX, Masters CL, Nonaka T, Hasegawa M, Bogoyevitch MA, Kanninen KM, Crouch PJ, White AR, (2011) C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress. Mol Neurodegener 6: 57
70. Milligan C, Gifondorwa D, (2011) Isolation and culture of postnatal spinal motoneurons. Methods Mol Biol 793: 77-85
71. Mitchell JC, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B, Tudor EL, Smith BN, Klasen C, Miller CC, Cooper JD, Greensmith L, Shaw CE, (2013) Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol 125: 273-288
72. Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, Russell SJ, Kirkland JL, Blackwell TK, Kahn CR, (2012) Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab 16: 336-347
73. Morlando M, Dini Modigliani S, Torrelli G, Rosa A, Di Carlo V, Caffarelli E, Bozzoni I, (2012) FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment. EMBO J 31: 4502-4510
74. Nandal A, Ruiz JC, Subramanian P, Ghimire-Rijal S, Sinnamon RA, Stemmler TL, Bruick RK, Philpott CC, (2011) Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2. Cell Metab 14: 647-657
75. Neumann M, Igaz LM, Kwong LK, Nakashima-Yasuda H, Kolb SJ, Dreyfuss G, Kretzschmar HA, Trojanowski JQ, Lee VM, (2007) Absence of heterogeneous nuclear ribonucleoproteins and survival motor neuron protein in TDP-43 positive inclusions in frontotemporal lobar degeneration. Acta Neuropathol 113: 543-548
76. Neumann M, Wang Y, Kim S, Hong SM, Jeng L, Bilgen M, Liu J, (2009) Assessing gait impairment following experimental traumatic brain injury in mice. J Neurosci Methods 176: 34-44
77. Nidadavolu LS, Niedernhofer LJ, Khan SA, (2013) Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxic stress. Aging 5: 460-473
78. Pare JM, LaPointe P, Hobman TC, (2013) Hsp90 cochaperones p23 and FKBP4 physically interact with hAgo2 and activate RNA interference-mediated silencing in mammalian cells. Mol Biol Cell 24: 2303-2310
79. Pelaez N, Carthew RW, (2012) Biological robustness and the role of microRNAs: a network perspective. Curr Top Dev Biol 99: 237-255
80. Pena JT, Sohn-Lee C, Rouhanifard SH, Ludwig J, Hafner M, Mihailovic A, Lim C, Holoch D, Berninger P, Zavolan M, Tuschl T, (2009) miRNA in situ hybridization in formaldehyde and EDC-fixed tissues. Nat Methods 6: 139-141
81. Peterson AC, Russell JD, Bailey DJ, Westphall MS, Coon JJ, (2012) Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol Cell Proteomics 11: 1475-1488
82. Qi HH, Ongusaha PP, Myllyharju J, Cheng D, Pakkanen O, Shi Y, Lee SW, Peng J, Shi Y, (2008) Prolyl 4-hydroxylation regulates Argonaute 2 stability. Nature 455: 421-424
83. Rabin SJ, Kim JM, Baughn M, Libby RT, Kim YJ, Fan Y, La Spada A, Stone B, Ravits J, (2009) Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology. Hum Mol Genet 19: 313-328
84. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, van den Bergh R, et al, (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362: 59-62
85. Saxena S, Cabuy E, Caroni P, (2009) A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci 12: 627-636
86. Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, Bostrom A, Theodoss J, Al-Nakhala BM, Vieira FG, Ramasubbu J, Heywood JA, (2008) Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 9: 4-15
87. Shan G, Li Y, Zhang J, Li W, Szulwach KE, Duan R, Faghihi MA, Khalil AM, Lu L, Paroo Z, Chan AW, Shi Z, Liu Q, Wahlestedt C, He C, Jin P, (2008) A small molecule enhances RNA interference and promotes microRNA processing. Nat Biotechnol 26: 933-940
88. Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim SO, Du Y, Wang Y, Chang WC, Chen CH, Hsu JL, Wu Y, Lam YC, James BP, Liu X, Liu CG, Patel DJ, Hung MC, (2013) EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature 497: 383-387
89. Shi H, Bencze KZ, Stemmler TL, Philpott CC, (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320: 1207-1210
90. Smalheiser NR, Zhang H, Dwivedi Y, (2014) Enoxacin elevates microRNA levels in rat frontal cortex and prevents learned helplessness. Front Psychiatry 5: 6
91. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE, (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319: 1668-1672
92. Tahbaz N, Kolb FA, Zhang H, Jaronczyk K, Filipowicz W, Hobman TC, (2004) Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. EMBO Rep 5: 189-194
93. Tortarolo M, Veglianese P, Calvaresi N, Botturi A, Rossi C, Giorgini A, Migheli A, Bendotti C, (2003) Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol Cell Neurosci 23: 180-192
94. Valdez G, Heyer MP, Feng G, Sanes JR, (2014) The role of muscle microRNAs in repairing the neuromuscular junction. PLoS ONE 9: e93140
95. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, et al, (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323: 1208-1211
96. Vance C, Scotter EL, Nishimura AL, Troakes C, Mitchell JC, Kathe C, Urwin H, Manser C, Miller CC, Hortobagyi T, Dragunow M, Rogelj B, Shaw CE, (2013) ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules. Hum Mol Genet 22: 2676-2688
97. Volkening K, Leystra-Lantz C, Yang W, Jaffee H, Strong MJ, (2009) Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Res 1305: 168-182
98. Waibel S, Neumann M, Rabe M, Meyer T, Ludolph AC, (2010) Novel missense and truncating mutations in FUS/TLS in familial ALS. Neurology 75: 815-817
99. Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH, (2009) TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci USA 106: 18809-18814
100. Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, Bassel-Duby R, Sanes JR, Olson EN, (2009) MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326: 1549-1554
101. Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-de Groote C, Van Broeckhoven C, Kumar-Singh S, (2010) TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci USA 107: 3858-3863
102. Wu C, So J, Davis-Dusenbery BN, Qi HH, Bloch DB, Shi Y, Lagna G, Hata A, (2011) Hypoxia potentiates microRNA-mediated gene silencing through posttranslational modification of Argonaute2. Mol Cell Biol 31: 4760-4774
103. Yang YM, Gupta SK, Kim KJ, Powers BE, Cerqueira A, Wainger BJ, Ngo HD, Rosowski KA, Schein PA, Ackeifi CA, Arvanites AC, Davidow LS, Woolf CJ, Rubin LL, (2013) A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell 12: 713-726
104. Zeng Y, Sankala H, Zhang X, Graves PR, (2008) Phosphorylation of Argonaute 2 at serine-387 facilitates its localization to processing bodies. Biochem J 413: 429-436
105. Zhang Z, Almeida S, Lu Y, Nishimura AL, Peng L, Sun D, Wu B, Karydas AM, Tartaglia MC, Fong JC, Miller BL, Farese RV Jr, Moore MJ, Shaw CE, Gao FB, (2013) Downregulation of microRNA-9 in iPSC-derived neurons of FTD/ALS patients with TDP-43 mutations. PLoS ONE 8: e76055